The effects of autonomous sensory meridian response (ASMR) on mood, attention, heart rate, skin conductance and EEG in healthy young adults.

Autonomous sensory meridian response (ASMR) is a warm tingling sensation which is often accompanied by feelings of calmness and relaxation. The present study examined the effects of an ASMR video on mood, attention, heart rate (HR), electrodermal activity (EDA), electroencephalography (EEG) and the interaction with personality factors in 38 young adults (33 females and 5 males). Based on the ASMR-checklist responses of having tingles during watching the ASMR video 15 participants out of 38 were classified as ASMR-experiencers. Mood, attention and personality characteristics were measured by the Profile of Mood States, the Flanker task and HEXACO. EEG, HR and EDA were recorded during the ASMR and control videos. Depressive feelings decreased after watching the ASMR video in individuals experiencing tingles relative to those not experiencing tingles. Furthermore, in all participants, irrespective of experiencing tingles, a decrease of HR during watching the ASMR video was found. In ASMR-experiencers scoring low on Conscientiousness EDA tended to increase and HR tended-relatively to the group not experiencing tingles-to decrease during watching the ASMR video. EEG recordings indicated that watching the ASMR video was associated with decreased alpha power in ASMR-sensitive participants and decreased theta as well as increased beta power in the whole group of participants. The observed ASMR-induced decrease of alpha and theta power and increase of beta power and (only in low conscientious participants) EDA may reflect that, apart from relaxation, ASMR is related to arousal and focused attention.

The Interrelationship between Insulin-Like Growth Factor 1, Apolipoprotein E ε4, Lifestyle Factors, and the Aging Body and Brain.

Aging is associated with a decrease in body and brain function and with a decline in insulin-like growth factor 1 levels. The observed associations between alterations in insulin-like growth factor 1 levels and cognitive functioning and Mild Cognitive Impairment suggest that altered insulin-like growth factor 1 signaling may accompany Alzheimer's disease or is involved in the pathogenesis of the disease. Recent animal research has suggested a possible association between insulin-like growth factor 1 levels and the Apolipoprotein E ε4 allele, a genetic predisposition to Alzheimer's disease. It is therefore hypothesized that a reduction in insulin-like growth factor 1 signaling may moderate the vulnerability to Alzheimer's disease of human Apolipoprotein E ε4 carriers. We address the impact of age-related decline of insulin-like growth factor 1 levels on physical and brain function in healthy aging and Alzheimer's disease and discuss the links between insulin-like growth factor 1 and the Apolipoprotein E ε4 polymorphism. Furthermore, we discuss lifestyle interventions that may increase insulin-like growth factor 1 serum levels, including physical activity and adherence to a protein rich diet and the possible benefits to the physical fitness and cognitive functioning of the aging population.

Adjunctive memantine in clozapine-treated refractory schizophrenia: an open-label 1-year extension study.

BACKGROUND: In a recent placebo-controlled, double-blind crossover trial (n = 52), significant beneficial effects on memory (d = 0.30) and negative symptoms (d = 0.29) were found after 12 weeks of memantine augmentation in patients with clozapine-refractory schizophrenia. In this open-label 1-year extension study we report the long-term effects and tolerability of memantine add-on therapy to clozapine. METHOD: Completers of the first trial who experienced beneficial effects during 12 weeks of memantine treatment received memantine for 1 year. Primary endpoints were memory and executive function using the Cambridge Neuropsychological Test Automated Battery, the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression Severity Scale (CGI-S). RESULTS: Of 31 randomized controlled trial completers who experienced beneficial effects from memantine, 24 received memantine for 1 year. The small improvement in memory found in the memantine condition in the placebo-controlled trial remained stable in the extension study. Executive function did not improve. After 26 weeks of memantine add-on therapy to clozapine, PANSS negative symptoms (r = 0.53), PANSS positive symptoms (r = 0.50) and PANSS total symptoms (r = 0.54) significantly improved. Even further significant improvement in all these measures was observed between 26 weeks and 52 weeks of memantine, with effect sizes varying from 0.39 to 0.51. CGI-S showed a non-significant moderate improvement at 26 weeks (r = 0.36) and 52 weeks (r = 0.34). Memantine was well tolerated without serious adverse effects. CONCLUSIONS: In the 1-year extension phase the favourable effect of adjunctive memantine on memory was sustained and we observed further improvement of negative, positive and overall symptoms in patients with clozapine-treated refractory schizophrenia.

Acute and short-term effects of caloric restriction on metabolic profile and brain activation in obese, postmenopausal women.

OBJECTIVE: Early anthropometric and metabolic changes during a caloric-restricted diet in obese postmenopausal women and correlations between these factors with activity in brain areas involved in processing of visual food related stimuli were investigated. SUBJECTS AND METHODS: An 8-week prospective intervention study of 18 healthy postmenopausal women, with a body mass index of 30-35 kg m-2. The first 2 weeks subjects were on an isocaloric diet and 4 weeks on a 1000 kcal restricted diet followed by 2 weeks on an isocaloric diet. Anthropometric and laboratory analyses were performed weekly during the isocaloric diet and three times a week during the caloric-restricted diet. Functional magnetic resonance imaging scans were obtained before and after the caloric restriction in four separate sessions (fasting or sated). Generalized Estimating Equations analysis was used for data analysis. RESULTS: A mean weight loss of 4.2±0.5 kg (4.8%) and a 4.2±0.4 cm decline in waist circumference were achieved. In the first week of caloric restriction, triglyceride, leptin, resistin and adiponectin levels as well as systolic blood pressure decreased and insulin-like growth factor-binding protein 1 levels increased. During and after weight loss, a significant increase in ghrelin levels was observed. Before weight loss, increased activation of the right amygdala was seen in response to food stimuli, and free fatty acids and glucose correlated with activity in various areas involved in food reward processing. After weight loss, fasting ghrelin and sated leptin levels correlated with activity in these areas. CONCLUSIONS: Already in the first week of caloric restriction in obese postmenopausal women, various favourable metabolic changes occur before clinically relevant weight loss is achieved. Activity in the amygdala region and correlations of metabolic factors with activity in brain areas involved in food reward processing differ substantially before and after weight loss.

Short and long-term effects of sham-controlled prefrontal EEG-neurofeedback training in healthy subjects.

OBJECTIVE: In this study we evaluated long-term effects of frontal beta EEG-neurofeedback training (E-NFT) on healthy subjects. We hypothesized that E-NFT can change frontal beta activity in the long-term and that changes in frontal beta EEG activity are accompanied by altered cognitive performance. METHODS: 25 healthy subjects were included and randomly assigned to active or sham E-NFT. On average the subjects underwent 15 E-NFT training sessions with a training duration of 45 min. Resting-state EEG was recorded prior to E-NFT training (t1) and in a 3-year follow-up (t3). RESULTS: Compared to sham E-NFT, which was used for the control group, real E-NFT increased beta activity in a predictable way. This increase was maintained over a period of three years post training. However, E-NFT did not result in significantly improved cognitive performance. CONCLUSION: Based on our results, we conclude that EEG-NFT can selectively modify EEG beta activity both in short and long-term. SIGNIFICANCE: This is a sham controlled EEG neurofeedback study demonstrating long-term effects in resting state EEG.

Supporting the generalist genes hypothesis for intellectual ability/disability: the case of SNAP25.

Intellectual disability (ID) is an unresolved health care problem with a worldwide prevalence rate of 2-3%. For many years, research into the genetic causes of ID and related disorders has mainly focused on chromosomal abnormalities or X-linked genetic deficits. Only a handful of autosomal genes are known to cause ID. At the same time it has been suggested that at least some cases of ID represent an extreme form of normal intellectual ability and therefore that genes important for intellectual ability in the normal range may also play a role in ID. In this study, we tested whether the autosomal SNAP25 gene, which was previously associated with variation in intellectual ability in the normal range, is also associated with ID. The gene product of SNAP25 is an important presynaptic plasma membrane protein, is known to be involved in regulating neurotransmitter release, and has been linked to memory and learning by its effect on long term potentiation in the hippocampus. Allele frequencies of two genetic variants in SNAP25 previously associated with intellectual ability were compared between a group of 636 ID cases (IQ < 70) and a control group of 361 persons of higher than average intellectual ability. We observed a higher frequency of the putative risk allele of rs363050 (P = 0.02; OR = 1.24) in cases as compared to controls. These results are consistent with a role of SNAP25 in ID, and also support the notion that ID reflects the lower extreme of the quantitative distribution of intellectual ability.

Early-stage cognitive impairment in Parkinson's disease and the influence of dopamine replacement therapy.

BACKGROUND AND PURPOSE: The aim of this study was to establish the cognitive profile of newly diagnosed untreated (de novo) patients with Parkinson's disease (PD) and more advanced, treated patients, and to determine the effects of dopamine (DA) replacement therapy. METHODS: A cohort of 23 de novo patients, 55 mild to moderately advanced, medicated PD patients and 21 healthy controls participated. Cognitive tests included the Cambridge Examination for Mental Disorders and a battery of neuropsychological tests taken from the Cambridge Neuropsychological Test Automated Battery and the Vienna Test System. RESULTS: De novo patients with PD were more impaired in working memory strategy use than healthy controls and treated patients with PD. Furthermore, the generation of random motor behaviour was more impaired in both de novo and treated PD patients than in healthy controls. Correlation analysis revealed that in treated patients with PD, ascending doses of dopaminergic medication were associated with poorer performance on a pattern recognition task. CONCLUSION: Selective impairments in strategy use and the generation of random motor behaviour are a very early feature of PD and might be of predictive value in further frontal cognitive deterioration. Furthermore, DA replacement therapy seems to improve frontal lobe function (strategy use) and worsen temporal lobe function (visual memory).

The relationship between IGF-I concentration, cognitive function and quality of life in adults with Prader-Willi syndrome.

Mental retardation is one of the clinical characteristics of Prader-Willi syndrome (PWS) and in part of the patients growth hormone deficiency is demonstrable. Cognitive function seems to be influenced by insulin-like growth factor I (IGF-I); however, little is known about cognitive function in relation to IGF-I levels in PWS adults. The aim of the present study was to evaluate cognitive function in adult PWS patients in comparison to healthy siblings and to investigate whether there is a correlation between cognitive function and IGF-I levels. Anthropometric measurements, IGF-I levels, quality of life (QoL), Appetite Assessment Score, IQ (GIT and Raven) and cognitive function (by four subtests of the Cambridge Neuropsychological Automated Testing Battery, CANTAB) were evaluated in PWS patients and their healthy siblings served as control group. PWS patients had significantly lower IGF-I levels, IQ and QoL when compared to controls. Reaction times were longer and performance was worse on CANTAB subtests in PWS adults. IGF-I on one hand and IQ, Appetite Assessment Score and cognitive performance on the other hand seem to be correlated in PWS patients. In conclusion, IGF-I levels, IQ and QoL are significantly lower in PWS subjects when compared to healthy siblings. In PWS adults, temporal as well as prefrontal cognitive functions are impaired. Higher IGF-I levels appear to be related to better intellectual skills and faster temporal memory processing in PWS patients.

Increased cortico-cortical functional connectivity in early-stage Parkinson's disease: an MEG study.

We set out to determine whether changes in resting-state cortico-cortical functional connectivity are a feature of early-stage Parkinson's disease (PD), explore how functional coupling might evolve over the course of the disease and establish its relationship with clinical deficits. Whole-head magnetoencephalography was performed in an eyes-closed resting-state condition in 70 PD patients with varying disease duration (including 18 recently diagnosed, drug-naive patients) in an "OFF" medication state and 21 controls. Neuropsychological testing was performed in all subjects. Data analysis involved calculation of three synchronization likelihood (SL, a general measure of linear and non-linear temporal correlations between time series) measures which reflect functional connectivity within (local) and between (intrahemispheric and interhemispheric) ten major cortical regions in five frequency bands. Recently diagnosed, drug-naive patients showed an overall increase in alpha1 SL relative to controls. Cross-sectional analysis in all patients revealed that disease duration was positively associated with alpha2 and beta SL measures, while severity of parkinsonism was positively associated with theta and beta SL measures. Moderately advanced patients had increases in theta, alpha1, alpha2 and beta SL, particularly with regard to local SL. In recently diagnosed patients, cognitive perseveration was associated with increased interhemispheric alpha1 SL. Increased resting-state cortico-cortical functional connectivity in the 8-10 Hz alpha range is a feature of PD from the earliest clinical stages onward. With disease progression, neighboring frequency bands become increasingly involved. These findings suggest that changes in functional coupling over the course of PD may be linked to the topographical progression of pathology over the brain.

Deficits in visuo-spatial working memory, inhibition and oculomotor control in boys with ADHD and their non-affected brothers.

Few studies have assessed visuo-spatial working memory and inhibition in attention-deficit/hyperactivity disorder (ADHD) by recording saccades and consequently little additional knowledge has been gathered on oculomotor functioning in ADHD. Moreover, this is the first study to report the performance of non-affected siblings of children with ADHD, which may shed light on the familiality of deficits. A total of 14 boys with ADHD, 18 non-affected brothers, and 15 control boys aged 7-14 years, were administered a memory-guided saccade task with delays of three and seven seconds. Familial deficits were found in accuracy of visuo-spatial working memory, percentage of anticipatory saccades, and tendency to overshoot saccades relative to controls. These findings suggest memory-guided saccade deficits may relate to a familial predisposition for ADHD.

Slowing of oscillatory brain activity is a stable characteristic of Parkinson's disease without dementia.

Extensive changes in resting-state oscillatory brain activity have recently been demonstrated using magnetoencephalography (MEG) in moderately advanced, non-demented Parkinson's disease patients relative to age-matched controls. The aim of the present study was to determine the onset and evolution of these changes over the disease course and their relationship with clinical parameters. In addition, we evaluated the effects of dopaminomimetics on resting-state oscillatory brain activity in levodopa-treated patients. MEG background oscillatory activity was studied in a group of 70 Parkinson's disease patients with varying disease duration and severity (including 18 de novo patients) as well as in 21 controls that were age-matched to the de novo patients. Whole head 151-channel MEG recordings were obtained in an eyes-closed resting-state condition. Levodopa-treated patients (N = 37) were examined both in a practically defined 'OFF' as well as in the 'ON' state. Relative spectral power was calculated for delta, theta, low alpha, high alpha, beta and gamma frequency bands and averaged for 10 cortical regions of interest (ROIs). Additionally, extensive clinical and neuropsychological testing was performed in all subjects. De novo Parkinson's disease patients showed widespread slowing of background MEG activity relative to controls. Changes included a widespread increase in theta and low alpha power, as well as a loss of beta power over all but the frontal ROIs and a loss of gamma power over all but the right occipital ROI. Neuropsychological assessment revealed abnormal perseveration in de novo patients, which was associated with increased low alpha power in centroparietal ROIs. In the whole group of Parkinson's disease patients, longer disease duration was associated with reduced low alpha power in the right temporal and right occipital ROI, but not with any other spectral power measure. No association was found between spectral power and disease stage, disease severity or dose of dopaminomimetics. In patients on levodopa therapy, a change from the 'OFF' to the 'ON' state was associated with decreases in right frontal theta, left occipital beta and left temporal gamma power and an increase in right parietal gamma power. Widespread slowing of oscillatory brain activity is a characteristic of non-demented Parkinson's disease patients from the earliest clinical stages onwards that is (largely) independent of disease duration, stage and severity and hardly influenced by dopaminomimetic treatment. Some early cognitive deficits in Parkinson's disease appear to be associated with increased low alpha power. We postulate a role for hypofunctional non-dopaminergic ascending neurotransmitter systems in spectral power changes in non-demented Parkinson's disease patients.

Oculomotor capture in ADHD.

It is generally thought that deficits in response inhibition form an important area of dysfunction in patients with attention-deficit/hyperactivity disorder (ADHD). However, recent research using visual search paradigms seems to suggest that these inhibitory deficits do not extend towards inhibiting irrelevant distractors. Using an oculomotor capture task, the present study investigated whether boys with ADHD and their nonaffected brothers are impaired in suppressing reflexive eye movements to a task-irrelevant onset distractor. Results showed that boys with ADHD had slower responses than controls, but were as accurate in their eye movements as controls. Nonaffected brothers showed similar problems in the speed of responding as their affected brothers, which might suggest that this deficit relates to a familial risk for developing the disorder. Importantly, all three groups were equally captured by the distractor, which shows that boys with ADHD and their brothers are not more distracted by the distractor than are controls. Saccade latency and the proportion of intrusive saccades were related to continuous dimensions of ADHD symptoms, which suggests that these deficits are not simply present or absent, but rather indicate that the severity of these deficits relate to the severity of ADHD. The finding that boys with ADHD (and their nonaffected brothers) did not have problems inhibiting irrelevant distractors contradicts a general response inhibition deficiency in ADHD, which may be explained by the relatively independency of working memory in this type of response inhibition.

Age-related cognitive effects of ECT and ECT-induced mood improvement in depressive patients.

This explorative study investigated the interaction between electroconvulsive therapy (ECT) treatment-effect, reduced depression, and neuropsychological outcome in relation to age. Follow-up neuropsychological assessment was conducted with depressive patients treated with ECT. From a potential sample of 45 patients, the neuropsychological measures (pre-ECT, three times post-ECT, up to 12 months) and clinical data from the remaining 21 patients who completed all assessments were evaluated (mean age=56.76; SD=14.12; range, 33-79). ECT resulted in a decrease in the depression scores. A distinct impact of ECT and depression decrease on cognitive domains was found. Depression alleviation was mainly associated with improvement in cognitive domains such as memory, information processing, and executive function. ECT improved cognitive domains such as information processing and perception. Short-term cognitive improvement was greater in older patients but showed an increase similar to that at long-term follow-up in younger patients (<60). Current findings provide evidence that ECT may improve cognitive functioning in nondemented elderly, which has strong clinical relevance concerning the use of ECT.

The relation between insulin-like growth factor I levels and cognition in healthy elderly: a meta-analysis.

OBJECTIVE: Insulin-like growth factor I (IGF-I) levels and cognitive functioning decrease with aging. Several studies report positive correlations between IGF-I levels and cognitive functioning in healthy elderly. However, because of controversial data no definitive conclusions can be drawn concerning the relation between IGF-I and cognition. Therefore, we carried out a meta-analysis on studies that report on the relation between IGF-I and cognition in healthy elderly. DESIGN: We searched the electronic databases for articles about IGF-I and cognition. Studies from 1985 to January 2005 are included. Two reviewers independently extracted data on study design and cognitive outcomes. Thirteen studies on IGF-I and cognition in elderly, with a total number of 1981 subjects, met the inclusion criteria. On the data from these studies meta-analyses were carried out by means of the program Comprehensive Meta-analysis using a random effects model. RESULTS: Pooled effects show that IGF-I levels in healthy elderly have a positive correlation with cognitive functioning, which appeared to be mainly measured with the mini mental state examination (MMSE). The effect size is 0.6, which indicates the presence of a large positive relationship between IGF and cognition in healthy elderly. CONCLUSION: These meta-analyses showed an overall relationship between IGF-I levels and cognitive functioning in healthy elderly. Further studies should be performed to clarify the role of IGF-I substitution in preserving cognitive functions with aging.

Physical activity and executive functions in the elderly with mild cognitive impairment.

The primary goal of the present study was to examine whether in the elderly with mild cognitive impairment (MCI), the effect of physical activity measured directly following treatment, was reflected in an improvement in cognitive functioning in general or in executive functions (EF) in particular. Secondly, this study aimed to compare the effectiveness of two types of intervention, with varying intensities: walking and hand/face exercises. Forty-three frail, advanced elderly subjects (mean age: 86) with MCI were randomly divided into three groups, namely, a walking group (n=15), a group performing hand and face exercises (n=13), and a control group (n=15). All subjects received individual treatment for 30 minutes a day, three times a week, for a period of six weeks. A neuropsychological test battery, administered directly after cessation of treatment, assessed cognitive functioning. The results show that although a (nearly) significant improvement in tasks appealing to EF was observed in both the walking group and the hand/face group compared to the control group, the results should be interpreted with caution. Firm conclusions about the effectiveness of mild physical activity on EF in the oldest old can only be drawn after studies with larger number of subjects.

The influence of growth hormone (GH) substitution on patient-reported outcomes and cognitive functions in GH-deficient patients: a meta-analysis.

OBJECTIVE: The influence of growth hormone (GH) replacement on patient-reported outcomes (i.e., quality of life, health status and well-being) and cognitive functioning in GH-deficient adults is controversial. DESIGN: We carried out a meta-analysis of clinical trials concerning the influence of GH substitution on patient-reported outcomes and cognitive functions (studies were selected from 1985 to 2004). The results of individual studies were combined in a series of meta-analyses using a random effects model. Effects of GH replacement in GH-deficient adults were compared to baseline and/or placebo. RESULTS: Fifteen studies on GH and patient-reported outcomes were included (830 patients, follow-up 3-50 months). Four of these studies also provided data on cognitive functions (85 patients, follow-up 6-12 months). Relative to baseline, GH treatment is found to have a large effect on patient-reported outcomes at 3 months, a medium effect at 6 months and a small effect at 12 months. With respect to the median treatment duration of 6 months placebo appears to be as effective as GH substitution. Cognitive functioning does not improve after 6 months of GH substitution, relative to baseline. CONCLUSION: This meta-analysis provides no evidence that GH improves patient-reported outcomes in GH-deficient patients. As the amount of cognitive data was too limited to allow for comparisons with placebo, from the present meta-analysis no conclusions can be drawn with respect to the impact of GH treatment on cognition.

Deficits on Corsi's block-tapping task in early stage Parkinson's disease.

Cognitive deficits in Parkinson's disease (PD) include disturbances in working memory. We examined sequential visuo-spatial memory span by means of an adaptation of the Corsi Block-Tapping Task in groups of medicated (n=14) and non-medicated (n=15) patients with early stage PD, and in control subjects (n=22). A deficit in memory span was found in medicated patients with early stage PD relative to controls. There were no differences between non-medicated patients relative to either controls or medicated patients. A decrease in sequential visuo-spatial memory span appears to be a relatively early feature of PD and most likely reflects executive rather than mnemonic dysfunction.

Effects of an oral mixture containing glycine, glutamine and niacin on memory, GH and IGF-I secretion in middle-aged and elderly subjects.

Aging is associated with declining activity of the growth hormone-insulin-like growth factor-I (GH-IGF-I) axis and with a decrease in cognitive function. The stimulatory effect of an orally administered nutritional supplement, mainly containing glycine, glutamine and niacin on the GH-IGF-I axis and on mood and cognition was investigated. Forty-two healthy subjects (14 men and 28 women, aged 40-76 years) were enrolled in a randomised, double blind, placebo-controlled trial. They received 5 g of a nutritional supplement or placebo, twice daily orally for a period of 3 weeks. At baseline and after 3 weeks, blood was collected for measurement of serum GH and IGF-I levels and mood and cognitive function were tested. The nutritional supplement ingestion for 3 weeks was found to increase serum GH levels with 70% relatively to placebo, whereas circulating IGF-I levels did not change. Mean GH (+/- SD) increased in this group from 3.23 (+/- 4.78) to 4.67 mU/l (+/- 5.27) (p = 0.03). GH increase was not associated with improvement in mood or memory. Correlation analyses, however, revealed that individual increases in IGF-I, but not GH, were associated with improved memory and vigour. It is concluded that an oral mixture of glycine, glutamine and niacin can enhance GH secretion in healthy middle-aged and elderly subjects.

Nutritional intake and daily functioning of psychogeriatric nursing home residents.

BACKGROUND: The level of observed daily functioning in psychogeriatric nursing home patients may be related to nutrient intake and body weight. OBJECTIVE: Relationships between nutrient intake, weight and daily functioning were assessed in nursing home residents. DESIGN: A descriptive, correlational design added by a experimental (repeated measurements) model was used to compare 3-day food records of 90 elderly psycho-geriatric residents filled in by the caretakers every 8 weeks during a period of 6 months. Nutrient intakes and cognitive scores were averaged over the total investigation period and studied separately at week 0, 8, 16 and 24. High and a low nutrient intake groups were compared with respect to daily functioning, which was measured by a Dutch geriatric nursing scale, the Zorg Index geriatrie (ZIG). RESULTS: Body weight was higher in the high niacin, high vitamin B-6 and high vitamin C intake groups. Unexpectedly, higher vitamin intakes were associated with a worse daily functioning. Results are explained by the fact that patients with a lower cognitive level are more dependent on their caregivers, thereby receiving more help with eating. Consequently, more severely demented patients have a higher intake of energy and nutrients. CONCLUSION: In order to optimize the effect of dietary vitamin supplementation in the total severity range of psycho-geriatric residents, caregivers should also pay attention to the eating habits of less dependent patients.

Quality of life of growth hormone (GH) deficient young adults during discontinuation and restart of GH therapy.

The present study evaluates the effects of one year of discontinuation and one year of growth hormone (GH) treatment on quality of life (QoL) in young adults with childhood-onset growth hormone deficiency (CO-GHD). Twenty-two subjects (14 males, 8 females; 11 isolated growth hormone deficient [IGHD], 11 multiple pituitary hormone deficient [MPHD]), aged between 15 and 22 years, on ongoing GH treatment were assessed during one year of discontinuation. Thereafter, 9 of these patients, who were found to be still GH deficient (GHD), added by 11 newly recruited GHD patients who also were not treated in the preceding year (in total 10 males and 10 females, aged between 17 and 27, 5 IGHD, 15 MPHD), restarted GH treatment for one year. During discontinuation and restart of GH treatment somatic and psychological assessments took place every 6 months. In the first 6 months of the GH discontinuation period insulin-like growth factor I (IGF-I) level significantly declined whereas no further decrease in IGF-I was seen after month 6. The number of psychological complaints and depression increased only during the first 6 months of discontinuation. Across the 12-month of discontinuation tension increased in MPHD and decreased in IGHD patients. Only in the first 6 months of GH treatment IGF-I level increased, anxiety decreased and QoL improved. Depression scores tended to decrease across the 12 month treatment period. During the 2-year discontinuation and treatment period intra-subject IGF-I level was negatively correlated with depression, fatigue, tension and anxiety and positively with vigor and memory. At the end of the treatment period all psychometric parameters were similar or even improved compared to those at the start of the discontinuation period. It is concluded that one year discontinuation of GH treatment leads to a decrease in QoL within 6 months which effect is counteracted within 6 months after restart of GH treatment.